A bioartificial liver system is described that incorporates a cell reservoir and hepatocyte spheroids to both increase the number of and longevity of cells in the system.spheroid aggregates are formed from isolated hepatocytes using a method described here.
SUMMARY
The invention provides a bioartificial liver system with an increased number of hepatocytes and the ability to maintain normal liver metabolism during continuous operation due to which systems of the invention can improve the efficiency of exvivo liver assistance provided to a patient experiencing liver failure. the longevity and activity of the hepatocytes are improved as a reslult of the use of spheroids in systems. a system for treating a biological fluid (e.g., blood or plasma) from a mammal is included.
The main parts are:
a) a bioreactor that includes a selectively permeable barrier separating a fluid treatment compartment anda cell compartment;
b) a cell reservoir in fluid communication with the cell compartment of the bioreactor
c) a rocking device in contact with the cell reservoir to induce motion in fluid contained in the cell reservoir.
an access port that provides access to the cell reservoir can also be included. pumps for circulating a cell fluid through the cell compartment and the cell reservoir, ultrafiltration cartridge in fluid communication with the cell compartment eyc can also be the additions. The bioreactor further can include a biological fluid inlet and a biological fluid outlet, for communication between the fluid treatment compartment and the bloodstream of the mammal. The method of forming spheroid aggregates includes providing a reservoir having a plurality of hepatocytes in a cell medium; and rocking the plurality of hepatocytes at a frequency and for a durationsufficient for spheroid aggregates to form.

Clinical status of BAL devices
In many BAl devices under use, hollow fiber technology is used to
separate cellular and perfusion compartments and to
provide a basic scaffold for hepatocyte attachment.For example, the HepatAssist from
Circe Biomedical, integrates cyropreserved porcine
hepatocytes on collagen-coated microcarriers in their
cartridge as well as a charcoal column in the perfusion
circuit for removal of adsorbants. Specific
concerns of immune reaction, xenozoonosis, and tumorgenicity
have been successfully addressed to gain
regulatory approval for introduction to the clinic.

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